Oral poliovirus vaccine (OPV) rapidly loses infectivity and potency unless stored in a frozen state. Delivery of this vaccine would be greatly enhanced by the development of less stringent OPV storage conditions. Various laboratories throughout the world are attempting to stabilize the vaccine either by the addition of stabilizing compounds or the development of successful lyophilization procedures. We have sought to develop a lyophilization procedure for poliovirus. In contrast to some viral vaccines, poliovirus infectivity is severely diminished after lyophilization. We have evaluated different lyophilization conditions in conjunction with the addition of various substances prior to lyophilization in an attempt to devise a successful approach for poliovirus. Viral stability is assessed by an ELISA test for D-antigen and a plaque assay for infectivity. Inclusion of a lipid based reagent dramatically increases virus survival, by a factor of 1000x, resulting in 20-40% survival of infectivity after lyophilization. Further studies have raised the recovery of infectious virus to greater than 50% However, temperature stability studies have indicated that the lyophilized virus is not significantly different than virus in solution. Our current efforts are focused on improving the temperature stability of the lyophilized virus by using procedures that stabilize the capsid architecture of the virion without impairing the infectivity of the virus. The use of cleavable bifunctional protein cross linkers has shown promise. Successful stabilization of OPV to less stringent storage conditions would facilitate vaccine distribution, particularly in less developed areas, and promote the global eradication of poliomyelitis.